Acetaminophen (Page 2 of 5)

3 DOSAGE FORMS AND STRENGTHS

Acetaminophen Injection is a sterile, clear, colorless, non-pyrogenic, preservative free, isotonic formulation of acetaminophen intended for intravenous infusion. Each 100 mL single-dose flexible bag contains 1,000 mg acetaminophen (10 mg/mL).

4 CONTRAINDICATIONS

Acetaminophen is contraindicated:

  • in patients with known hypersensitivity to acetaminophen or to any of the excipients in the intravenous formulation.
  • in patients with severe hepatic impairment or severe active liver disease [see Warnings and Precautions (5.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Hepatic Injury

Administration of acetaminophen in doses higher than recommended may result in hepatic injury, including the risk of liver failure and death [see Overdosage (10)]. Do not exceed the maximum recommended daily dose of acetaminophen [see Dosage and Administration (2)]. The maximum recommended daily dose of acetaminophen includes all routes of administration and all acetaminophen-containing products administered, including combination products.

Use caution when administering acetaminophen in patients with the following conditions: hepatic impairment or active hepatic disease, alcoholism, chronic malnutrition, severe hypovolemia (e.g., due to dehydration or blood loss), or severe renal impairment (creatinine clearance ≤ 30 mL/min) [see Use in Specific Populations (8.6, 8.7)].

5.2 Serious Skin Reactions

Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

5.3 Risk of Medication Errors

Take care when prescribing, preparing, and administering acetaminophen injection in order to avoid dosing errors which could result in accidental overdose and death. In particular, be careful to ensure that:

  • the dose in milligrams (mg) and milliliters (mL) is not confused;
  • the dosing is based on weight for patients under 50 kg;
  • infusion pumps are properly programmed; and
  • the total daily dose of acetaminophen from all sources does not exceed maximum daily limits [see Dosage and Administration (2)].

5.4 Allergy and Hypersensitivity

There have been post-marketing reports of hypersensitivity and anaphylaxis associated with the use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, and pruritus. There were infrequent reports of life-threatening anaphylaxis requiring emergent medical attention. Discontinue acetaminophen immediately if symptoms associated with allergy or hypersensitivity occur. Do not use acetaminophen in patients with acetaminophen allergy.

6 ADVERSE REACTIONS

The following serious adverse reactions are discussed elsewhere in the labeling:

  • Hepatic Injury [see Warnings and Precautions (5.1)]
  • Serious Skin Reactions [see Warnings and Precautions (5.2)]
  • Allergy and Hypersensitivity [see Warnings and Precautions (5.4)]

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in practice.

Adult Population

A total of 1,020 adult patients have received acetaminophen in clinical trials, including 37.3% (n=380) who received 5 or more doses, and 17% (n=173) who received more than 10 doses. Most patients were treated with acetaminophen 1,000 mg every 6 hours. A total of 13.1% (n=134) received acetaminophen 650 mg every 4 hours.

All adverse reactions that occurred in adult patients treated with either acetaminophen or placebo in repeated dose, placebo-controlled clinical trials at an incidence ≥ 3% and at a greater frequency than placebo are listed in Table 3. The most common adverse events in adult patients treated with acetaminophen (incidence ≥ 5% and greater than placebo) were nausea, vomiting, headache, and insomnia.

Table 3. Treatment-Emergent Adverse Reactions Occurring in ≥ 3% of Acetaminophen- treated Adult Patients and at a Greater Frequency than Placebo in Placebo-Controlled, Repeated Dose Studies

* Pyrexia adverse reaction frequency data is included in order to alert healthcare practitioners that the antipyretic effects of acetaminophen may mask fever.

System Organ Class — Preferred Term Acetaminophen (N=402) n (%) Placebo (N=379) n (%)
Gastrointestinal Disorders Nausea Vomiting 138 (34)62 (15) 119 (31)42 (11)
General Disorders and Administration Site Conditions Pyrexia* 22 (5) 52 (14)
Nervous System Disorders Headache 39 (10) 33 (9)
Psychiatric Disorders Insomnia 30 (7) 21 (5)

Other Adverse Reactions Observed During Clinical Studies of Acetaminophen in Adults

The following additional treatment-emergent adverse reactions were reported by adult subjects treated with acetaminophen in all clinical trials (n=1,020) that occurred with an incidence of at least 1% and at a frequency greater than placebo (n=525).

Blood and lymphatic system disorders: anemia

General disorders and administration site conditions: fatigue, infusion site pain, edema peripheral

Investigations: aspartate aminotransferase increased, breath sounds abnormal

Metabolism and nutrition disorders: hypokalemia

Musculoskeletal and connective tissue disorders: muscle spasms, trismus

Psychiatric disorders: anxiety

Respiratory, thoracic and mediastinal disorders: dyspnea

Vascular disorders: hypertension, hypotension

Pediatric Population

A total of 355 pediatric patients (47 neonates, 64 infants, 171 children, and 73 adolescents) have received acetaminophen in active-controlled (n=250) and open-label clinical trials (n=225), including 59.7% (n=212) who received 5 or more doses and 43.1% (n=153) who received more than 10 doses. Pediatric patients received acetaminophen doses up to 15 mg/kg on an every 4 hours, every 6 hours, or every 8 hours schedule. The maximum exposure was 7.7, 6.4, 6.8, and 7.1 days in neonates, infants, children, and adolescents, respectively.

The most common adverse events (incidence ≥ 5%) in pediatric patients treated with acetaminophen were nausea, vomiting, constipation, pruritus, agitation, and atelectasis.

Other Adverse Reactions Observed During Clinical Studies of Acetaminophen in Pediatrics The following additional treatment-emergent adverse reactions were reported by pediatric subjects treated with acetaminophen (n=355) that occurred with an incidence of at least 1%.

Blood and lymphatic system disorders: anemia

Cardiac disorders: tachycardia

Gastrointestinal disorders: abdominal pain, diarrhea

General disorders and administration site conditions: pyrexia, injection site pain, edema peripheral

Metabolism and nutrition disorders: hypokalemia, hypomagnesemia, hypoalbuminemia, hypophosphatemia, hypervolemia

Musculoskeletal and connective tissue disorders: muscle spasm, pain in extremity

Nervous system disorders: headache

Psychiatric disorders: insomnia

Renal and urinary disorders: oliguria

Respiratory, thoracic and mediastinal disorders: hypoxia, pleural effusion, pulmonary edema, stridor, wheezing

Skin and subcutaneous tissue disorders: periorbital edema, rash

Vascular disorders: hypotension, hypertension

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